Patients with congestive heart failure (CHF) have been noted in small clinical trials to have increased plasma homocysteine levels. Vasan and colleagues hypothesized that, given experimental evidence showing the vulnerability of myocardial tissue to homocysteine-induced injury, elevated plasma homocysteine levels would increase the risk for CHF.

Participants included Framingham Heart Study subjects who were free of CHF and who had plasma homocysteine levels determined at two examinations eight years apart. The 2,491 eligible subjects, including 1,547 women, were examined every two years.

About one quarter of patients had baseline homocysteine levels of more than 1.9 mg per L (14 mmol per L). During an eight-year follow-up, 156 subjects (88 women) developed CHF. Crude cumulative incidence of CHF in women and men in the top two homocysteine quartiles was considerably higher than the incidence in the lower two quartiles. An age-adjusted model showed similar results; CHF risk increased about 25 percent in men and 49 percent in women per quartile. In women, the risk of CHF rose at the second quartile and continued to increase. In men, CHF risk increased only beyond the second quartile.

This study appears to show that in women, elevated plasma homocysteine concentration is related positively and strongly to CHF risk. In men, the association of plasma homocysteine with risk of CHF became evident only at values exceeding the median. The authors state that if their observational findings are confirmed, additional studies will have to show that lowering homocysteine levels with folic acid can reduce CHF risk.